Effects of L-arginine and L-citrulline Supplementation on Muscle Respiration

The Effect of L-arginine and L-citrulline Supplementation on Endurance Performance and Mitochondrial Respiration

The objective of this trial is to determine the effects of dietary supplementation with the amino acids, L-arginine and L-citrulline, on endurance performance and mitochondrial respiration in healthy men compared to supplementation with L-arginine alone and a placebo supplement.

Study Overview

• Status: Completed
• Conditions: Dietary Exposure
• Intervention / Treatment: Dietary supplement: Dietary Supplement; Behavioral: Endurance exercise on a cycle ergometer

Detailed Description

This study is a randomized, double-blind, cross over trial of L-arginine and L-citrulline supplementation, L-arginine supplementation alone and placebo supplementation in healthy men. The intervention period will be 8-11 weeks for each participant and a minimum of 15 individuals will be recruited and enrolled to complete the trial. Subjects will complete the experimental protocol described below over 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks. Subjects will ingest corn-starch as a placebo, L-arginine (3g/day) or L-arginine (1.5 g/day) + L-citrulline (1.5g/day). On day 7 of the supplementation period, a skeletal muscle biopsy and blood sample will be obtained from the subjects to investigate mitochondrial function and blood amino acid and nitric oxide levels. On day 10 of the supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance. These assessments will be performed to determine the effects of co-ingesting L-arginine and L-citrulline compared to L-arginine alone and placebo administration.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Leicester
    • Loughborough, Leicester, United Kingdom, Le11 3YU
      • School of Sport, Exercise and Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy male, 18-40 years of age
• recreationally-active
• healthy BMI (≥18.5 and ≤24.9 kg/m2)

Exclusion Criteria:

• participating in other studies currently or in the past two months or has an intention to participate in other studies over the period of this study
• history of gastric, digestive, cardiovascular, renal disease or any other orthopaedic diseases related to motor organs
• lidocaine allergy
• use of medication that may affect study measures
• contraindication to the biopsy procedures
• on medications that affect the immune system
• on Aspirin or other drugs known to prolong bleeding
• smoker
• user of dietary supplements currently or in the past one month
• a heavy drinker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-arginine and L-citrulline; 10 days of supplementation with 1.5 g of L-arginine and 1.5 g of L-citrulline per day	Dietary supplement: Dietary Supplement; Dietary Supplement: L-arginine and L-citrulline supplement, L-arginine supplement, or placebo supplement (corn-starch) Subjects will complete 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks.; Behavioral: Endurance exercise on a cycle ergometer; On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.
Experimental: L-arginine; 10 days of supplementation with 3 g of L-arginine per day	Dietary supplement: Dietary Supplement; Dietary Supplement: L-arginine and L-citrulline supplement, L-arginine supplement, or placebo supplement (corn-starch) Subjects will complete 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks.; Behavioral: Endurance exercise on a cycle ergometer; On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.
Placebo Comparator: Placebo (corn-starch); 10 days of supplementation with corn-starch	Dietary supplement: Dietary Supplement; Dietary Supplement: L-arginine and L-citrulline supplement, L-arginine supplement, or placebo supplement (corn-starch) Subjects will complete 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks.; Behavioral: Endurance exercise on a cycle ergometer; On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endurance performance on a cycle ergometer between L-arginine supplementation and placebo supplementation	On day 10 of the supplementation periods, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance	8-11 weeks
Change in Endurance performance on a cycle ergometer between L-arginine + L-citrulline supplementation and placebo supplementation	On day 10 of the supplementation periods, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance	8-11 weeks
Changes of mitochondrial function in skeletal muscle between L-arginine supplementation and placebo supplementation	On day 7 of the supplementation periods, a skeletal muscle biopsy sample will be obtained from subjects to investigate mitochondrial function.	8-11 weeks
Changes of mitochondrial function in skeletal muscle between L-arginine + L-citrulline supplementation and placebo supplementation	On day 7 of the supplementation periods, a skeletal muscle biopsy sample will be obtained from subjects to investigate mitochondrial function.	8-11 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of amino acid and nitric oxide biomarkers levels in plasma between L-arginine supplementation and placebo supplementation	On days 7 and 10 of the supplementation periods, a venous blood sample will be obtained from subjects to investigate amino acid and nitric oxide biomarkers levels in plasma.	8-11 weeks
Changes of amino acid and nitric oxide biomarkers levels in plasma between L-arginine + L-citrulline supplementation and placebo supplementation	On days 7 and 10 of the supplementation periods, a venous blood sample will be obtained from subjects to investigate amino acid and nitric oxide biomarkers levels in plasma.	8-11 weeks
Changes in muscle oxygenation between L-arginine supplementation and placebo supplementation	On day 10 of the supplementation periods, skeletal muscle oxygenation will be assessed using near-infrared spectroscopy to reveal the tissue saturation index during exercise.	8-11 weeks
Changes in muscle oxygenation between L-arginine + L-citrulline supplementation and placebo supplementation	On day 10 of the supplementation periods, skeletal muscle oxygenation will be assessed using near-infrared spectroscopy to reveal the tissue saturation index during exercise.	8-11 weeks
Changes in subjective feeling during and after exercise between L-arginine supplementation and placebo supplementation	On day 10 of the supplementation period, subjective feeling during (using the 6-20 ratings of perceived exertion scale) and after (using a 100 mm visual analogue scale where 0 mm = no pain and 100 m = maximal pain) exercise will be assessed. Subjective feeling will also be assessed on the morning of day 11 of each supplementation period.	8-11 weeks
Changes in subjective feeling during and after exercise between L-arginine + L-citrulline supplementation and placebo supplementation	On day 10 of the supplementation period, subjective feeling during (using the 6-20 ratings of perceived exertion scale) and after (using a 100 mm visual analogue scale where 0 mm = no pain and 100 m = maximal pain) exercise will be assessed. Subjective feeling will also be assessed on the morning of day 11 of each supplementation period.	8-11 weeks

Collaborators and Investigators

• Sponsor: Loughborough University
• Collaborators: Kyowa Hakko Bio Co., Ltd.
• Investigators: Principal Investigator: Stephen J Bailey, PhD, lecturer

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 26, 2019

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: L-arginine; Mitochondrial function; L-citrulline; Healthy males; Endurance performance
• Other Study ID Numbers: R19-P010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No